Peptidyl leukotrienes signal through at least three cysteinyl leukotriene receptors. The control of expression of these two receptors is not well understood. The current project will propose to study the effect of proinflammatory cytokines on gene and protein expression of cysLTR1 and cysLTR2 receptors in human cells. The structure of the two genes and of the 5' promoter region of each has been determined. Assays of gene expression, steady state mRNA expression, and cellular protein expression have been developed. Human cell lines, which express either LTR1 or LTR2 are being studied. The interaction of signaling by LTD4 and LTB4 is being studied in human monocytes. In addition, treatment of macrophages with low molecular weight hyaluronic acid down regulates cysLTR1 message and down regulates cysLTR1 signaling.